The overall goal of this project is to determine the roles that neuropeptide Y and POMC neuronal systems play regulating food intake in primate species. Neuropeptide Yis a very potent orexigenic agent in rodents, and POMC neurons that produce a-MSH appear to be in a position to play a key role in the inhibition of food intake in rodents, by acting through melanocortin type 4 (MC4) receptors. An interesting link between these systems has recently been established by our studies showing that in the rat arcuate nucleus NPY neurons contain mRNA for agouti-related peptide, AGRP, which is an endogenous inhibitor of the MC4 receptor. In contrast to the large number of studies seeking central neural systems that control food intake in rodents species, very little work has been done in primate species to determine if the control of food intake in the primate is similar to that in the rat. We have recently shown that administration of NPY can stimulate food intake in the adult male rhesus monkey, but that the feeding sensitive NPY system in the primate is much more complex than in the rat. The goal of the project we propose in this grant is to continue our studies in the non-human primate to determine (a) the degree to which food intake is controlled by NPY and POMC systems, (b) which population(s) of NPY and POMC neurons modulate food intake in the primate, and (c) what metabolic and neural signals regulate NPY and POMC lean primates. Increased understanding of the neural systems controlling food intake in the primate will provide important new information that will e useful in devising new treatments for obesity, a condition that leads to a large increase in human morbidity and mortality, resulting from an increased incidence of cardiovascular disease, stroke, diabetes, and associated problems in vision, kidney and liver function. Converse, this information will also be of utility in designing new treatments for people with life-threatening eating disorders, including anorexia and bulimia nervosa.